Abstract
SARS-CoV-2 induces a muted innate immune response compared to other respiratory viruses. Mitochondrial dynamics might partially mediate this effect of SARS-CoV-2 on innate immunity. Polypeptides encoded by open reading frames of SARS-CoV and SARS-CoV-2 have been shown to localize to mitochondria and disrupt Mitochondrial Antiviral Signaling (MAVS) protein signaling. Therefore, we hypothesized that SARS-CoV-2 would distinctly regulate the mitochondrial transcriptome. We analyzed multiple publicly available RNASeq data derived from primary cells, cell lines, and clinical samples (i.e., BALF and lung). We report that SARS-CoV-2 did not dramatically regulate (1) mtDNA-encoded gene expression or (2) MAVS expression, and (3) SARS-CoV-2 downregulated nuclear-encoded mitochondrial (NEM) genes related to cellular respiration and Complex I.
Highlights
SARS-CoV-2 induces a muted innate immune response compared to other respiratory viruses
Our analyses showed that the mitochondrial transcriptome signature of SARS-CoV-2 infection included both shared and independent biological processes from influenza A virus (IAV), HPIV, and RSV
We found that SARS-CoV-2 did not induce a dramatic mtDNA-encoded gene expression signature in NHBE, A549, and Calu-3 cells
Summary
SARS-CoV-2 induces a muted innate immune response compared to other respiratory viruses. Polypeptides encoded by open reading frames of SARS-CoV and SARS-CoV-2 have been shown to localize to mitochondria and disrupt Mitochondrial Antiviral Signaling (MAVS) protein signaling. SARS-CoV-2 infection induced low IFN-I and IFN-III levels across multiple cellular models This specific attenuated innate immune response could explain how older individuals, who are likely to present age-related immune cell decline, are at risk for SARS-CoV-2 mortality. Host cell innate immunity is regulated by the Mitochondrial Antiviral Signaling protein (MAVS)[5, 6]. Mitochondria-associated ER membranes and nearby mitochondria become tethered by MFN2 and RIG-1, forming a complex that recruits TRIM25 and the molecular chaperone 14-3-3e into a translocon structure[8] This translocon localizes to the mitochondrion and binds MAVS, after which MAVS interacts with TANK binding kinase 1, IKKA, and I KKB9. We assessed the effect of SARS-CoV-2 on the mitochondrial transcriptome by reanalyzing publicly available RNASeq data
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